Obesity is a burgeoning public health problem that is associated with an adverse metabolic profile and higher levels of morbidity and mortality from multiple causes. Current methods for assessing obesity focus on either nonspecific measures of overall body weight (i.e. body mass index) or the extent of abdominal ("central") adiposity. Recent studies indicate that other measures of body composition, including lean muscle and intermuscular, liver and pericardial fat, are correlated with adipocytokines and atherosclerotic cardiovascular disease (CVD). Notably, some evidence suggests that muscle tissue measures may be related to systemic inflammation, perhaps via mediators common to adiposity. Additionally, recent evidence suggests that the failure to develop adequate adipose tissue mass (lipodystrophy) and instead storing fat ectopically (i.e. in the liver, pericardium and muscle) is associated with severe insulin resistance and diabetes. However, it remains unclear what measures (i.e. lean muscle, intermuscular fat, pericardial fat) are most relevant to the link between adipocyokines/inflammation and CVD, and how such effects vary across sex and ethnic specific subgroups. We propose to evaluate the tissue composition of the abdomen, liver, and pericardium in 798 men and women who are being studied in the Rancho Bernardo Study (RBS). The RBS is a prospective cohort study of over 30 years that has an extensive database of demographic and survey information as well as biomarker material on each participant. The RBS includes participants from 3 ethnic groups (Caucasians, African Americans and Filipinos) who had electron beam computed tomography (EBCT) scans of the chest and abdomen for coronary artery calcium (CAC) and visceral fat (VF), respectively. Six hundred eleven (611) of these participants had repeat EBCT scans of the chest and abdomen to assess changes in CAC and visceral fat. Using both the "baseline" and "follow-up" abdominal EBCT scans and specially designed software, we will calculate eight discrete measures of body composition from the scans: VF, subcutaneous fat, intermuscular fat, abdominal muscle, VF to visceral cavity size ratio, muscle/visceral fat ratio, liver fat and pericardial fat. We will test for associations between these measures and four inflammatory adipocytokines (interleukin-6, tumor necrosis factor - 1, leptin, adiponectin), CVD risk factors, and CAC. The cross-sectional analyses will explore the link between the fat and muscle measures and adipocytokines and the degree to which such links explain the association between measures of fat/muscle and CAC. We will also explore how sex and ethnicity are related to these associations and whether these variables modify the nature of the associations. The prospective component of the study will use the same conceptual model, but we will determine associations between both baseline and prospective changes in abdominal body composition and changes in CAC. Modification by sex, ethnicity, and mediation by adipocytokines will be evaluated. In summary, this innovative study design will collect and analyze a wealth of rigorously validated data to explore the links between different measures of adiposity and muscle, adipocytokines, and subclinical CVD. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE/RELEVANCE Obesity is a growing public health problem that is associated with changes in the body's metabolism, as well as higher levels of disease and death from multiple causes. We propose to evaluate the tissue composition of the abdomen, liver, and pericardium in 798 men and women who are being studied in the Rancho Bernardo Study (RBS). This innovative study will collect and analyze a wealth of rigorously validated data to explore the links between different measures of fat and muscle in the abdomen, liver, and pericardium, adipocytokines, and subclinical cardiovascular disease.